Activation of spinal kainate receptors after inflammation: behavioral hyperalgesia and subunit gene expression.

Abstract

We determined whether neural responses to inflammation and hyperalgesia involve activation of kainate receptors, a subgroup of glutamate receptors. Inflammation was introduced into the hind paw by intraplantar injection of complete Freund's adjuvant. The inflammation-induced thermal hyperalgesia was attenuated by intrathecal administration of a non-selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX), as well as by selective kainate receptor antagonists, 6,7,8,9-tetrohydro-5-nitro-1H-benz[g]indole-2,3-dione 3-oxime (NS-102) and 3S,4aR,6S,8aR-6-(4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-deca-hydroisoquinoline-3-carboxylic acid (LY382884). Reverse transcription-polymerase chain reaction (RT-PCR) indicated that the GluR5 and GluR6, but not the GluR7, KA1 and KA2 subunits, exhibited increased mRNA expression at 2 h to 3 days following inflammation (P<0.05). Western blot showed an increase in GluR6 protein levels (P<0.01) with a time course consistent with the changes in its mRNA levels. cDNA sequence and BbvI endonuclease digestion of the GluR6 PCR product revealed that the upregulated GluR6 mRNAs were predominantly the unedited form (Q). These results suggest that a selective upregulation of kainate receptor subunit expression contributes to inflammatory hyperalgesia.

• Authors: Wei Guo, Shiping Zou, Michael Tal, Ke Ren
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 452 Issue 3 Pg. 309-18 (Oct 11 2002) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12359272 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Kainic Acid

Topics

• Amino Acid Sequence (physiology)
• Animals
• Gene Expression Regulation (drug effects, physiology)
• Hyperalgesia (genetics, metabolism)
• Inflammation (genetics, metabolism)
• Male
• Molecular Sequence Data
• Pain Measurement (drug effects, methods)
• Psychomotor Performance (physiology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Kainic Acid (antagonists & inhibitors, biosynthesis)
• Spinal Cord (metabolism)